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The review editor sent me a book to review for Gut with holidays looming. He left a week before me and is currently observing whales off the east cost of the USA where I hope he will encounter the albino whale. I, on the other hand, am in a more peaceful location surrounded by the truly magnificent lochs, standing stones, stone circles, chambered cains, duns, and crannogs on the Outer Hebridean island of North Uist.
The book Therapeutic Roles of Selective COX-2 Inhibitors is the latest in a series of similar books edited by Vane and Bolting, and I have found it in many ways as interesting and extraordinary as my surroundings. It exceeded all expectations, bringing together some of the people that have driven the COX-2 story through from birth of a concept to a marketable drug.
Vane and Botting set the pace with an authoritative introduction, elegantly outlining the history, biochemistry, and physiology of COX inhibition and its clinical potential. In this book they gracefully allow etodolac and nimesulide into the privileged COX-2 selective club or, as they call it, the “COX-1 sparing drug” club. Then follow high quality chapters on the discovery and studies on rofecoxib and celecoxib along with discussions on the various test systems to assess selectivity. The excitement of reading Derek Willoughby’s chapter on COX-2 in inflammation in experimental models kept me awake for the whole night. This is a true master at work!
At last (Ballou et al) a detailed and intelligent account of the lessons that we should have learned from the study of COX-1 and -2 deficient animals. Indeed the knee jerk response, if not silence, to “unexpected” data obtained from these animals, such as the lack of gastrointestinal damage in COX-1 knockouts, simply allows prevailing simplistic theories on the role of the two enzymes to be maintained a bit longer. The following chapters on enzymes in nocioception, Alzheimer’s disease, kidney, apoptosis, labour, cardiovascular system, arthritis, and bone are a treat, and reflect the scope of the book. Whittle, Hawkey, and Roderiguez could have combined their three chapters on the gastrointestinal toxicity of NSAIDs as their knowledge is complementary. They invade each others “intellectual” territory which gives the impression of conflict and confusion where none exists. The chapter by DuBois on COX-2 in colorectal cancer is only disappointing because of its brevity; the man has so much more knowledge to share! However, this is partially compensated by an excellent review of the role of COX-2 in other cancers. The book ends with rather biased accounts on the virtues of each of the COX-2 selective agents.
This book is currently the best available reference source on a subject that is growing in importance and complexity. The only irritations are some unnecessary self congratulatory comments and unashamed pleas for financial support that will raise the eyebrows of the purchaser of this book in Hay-on-Wye bookshops at the end of this century. I can thoroughly recommend it for all established prostaglandin and COX researchers, and PhD students. Clinical gastroenterologists will find something new of interest. Those with time, concentration, and a biochemical background will surely enjoy this book as much as I did.
Aah! Catherine my lifelong companion has just brought me a wee dram (Talisker single malt whisky with 10% v/v local water). Life just does not get much better than this. My euphoria is however marred by the knowledge that the COX-2 selective drugs are not available to the citizens of Cuba as a result of the USA’s embargo.
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